The concept of cancer as a stem cell disease has slowly gained ground over the last decade. A 'stem-like' state essentially necessitates that some cells in the developing tumor express the properties of remaining quiescent, self-renewing and regenerating tumors through establishment of aberrant cellular hierarchies. Alternatively, such capacities may also be reacquired through a de-differentiation process. The abnormal cellular differentiation patterns involved during either process during carcinogenesis are likely to be driven through a combination of genetic events and epigenetic regulation. The role(s) of the latter is increasingly being appreciated in acquiring the requisite genomic specificity and flexibility required for phenotypic plasticity, specifically in a context wherein genome sequences are not altered for differentiation to ensue. In this chapter, the recent advances in elucidating epigenetic mechanisms that govern the self-renewal, differentiation and regenerative potentials of cancer stem cells will be presented.